Perioperative Neurocognitive Disorder

Eckenhoff, Roderic G.; Maze, Mervyn; Xie, Zhongcong; Culley, Deborah J.; Goodlin, Sarah J.; Zuo, Zhiyi; Wei, Huafeng; Whittington, Robert A.; Terrando, Niccolò; Orser, Beverley A.; Eckenhoff, Maryellen F.

doi:10.1097/aln.0000000000002956

Cited by 118 publications

(87 citation statements)

References 121 publications

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“…A total of 110 adults were recruited in this study (Figure 1). Patients were excluded if they: (Daiello et al, 2019) had a past medical history of neurological disease such as delirium, schizophrenia, dementia, or stroke [with regard to dementia, it was screened if Mini Mental State Examination (MMSE) scores of ≤ 17 for illiterate patients, ≤ 20 for patients with 1-6 years of education, or ≤ 24 for patients with 7 or more years of education] (Li et al, 2016;Vutskits and Xie, 2016) were unable to read or write or cooperate; (Eckenhoff et al, 2020) had a history of drug or alcohol abuse. Eighty participants (15 POD vs. 65 Non-POD) completed the study.…”

Section: Patients and Settingmentioning

confidence: 99%

“…Patients over 65 years of age are the largest consumers of procedural care, and postoperative delirium (POD) is one of the most common complications experienced by elderly patients during the postoperative period (Daiello et al, 2019). POD is an acute neuropsychiatric syndrome occurring in the hours to days after anesthesia and surgery (Vutskits and Xie, 2016), which can elicit durable deficits in executive function, memory, attention, and other cognitive domains (Eckenhoff et al, 2020). The incidence of POD is 20-45% among elderly adult surgery patients (Rudolph and Marcantonio, 2011;Inouye et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Han

Zhang

Liu

et al. 2020

Front. Aging Neurosci.

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Objective: To investigate dysregulated molecules in preoperative cerebrospinal fluid (CSF) of elderly hip fracture patients with postoperative delirium (POD), in order to identify potential pathological mechanisms and biomarkers for pre-stage POD. Materials and Methods: This nested case control study used untargeted metabolomic and lipidomic analysis to profile the preoperative CSF of patients (n = 40) who developed POD undergone hip fracture surgery (n = 10) and those who did not (n = 30). Thirty Non-POD patients were matched to 10 POD patients by age (± 2 years) and Mini Mental State Examination score (± 2 points). CSF was collected after successful spinal anesthesia and banked for subsequent analysis. On the first two postoperative days, patients were assessed twice daily using the Confusion Assessment Method-Chinese Revision. CSF samples from the two groups were analyzed to investigate possible relevant pathological mechanisms and identify candidate biomarkers. Results: Demographic characteristics of the groups were matched. Eighteen metabolites and thirty-three lipids were dysregulated in the preoperative CSF of POD patients. Pathway enrichment analysis revealed perturbations in D-glutamine and D-glutamate metabolism; glycerophospholipid metabolism; alanine, aspartate and glutamate metabolism; sphingolipid metabolism; histidine metabolism; and arginine biosynthesis at the pre-delirium stage. Receiver operating characteristic curve analysis indicated that phosphatidylethanolamine (PE, 40:7e), with an area under the curve value of 0.92, is a potential biomarker for POD. Conclusion: Multiple pathological mechanisms in the POD group were involved before surgery, including neuroinflammation, oxidative stress, and energy metabolism disorders induced by hypoxia, as well as neurotransmitter imbalances such as increased dopamine and glutamate, and decreased glutamine. These metabolic abnormalities potentially increase the fragility of the brain, thus contributing to POD. PE (40:7e) might

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Section: Patients and Settingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Han

Zhang

Liu

et al. 2020

Front. Aging Neurosci.

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“…Perioperative neurocognitive disorders (PND), encompassing acute delirium and longer-lasting postoperative cognitive dysfunction, are the most common and least recognized complications of surgery and anesthesia in older patients (Subramaniyan and Terrando, 2019;Eckenhoff et al, 2020). The incidence of PND varies from 41 to 75% at 7 days to 18-45% at 3 months post-surgery (Deo et al, 2011;Skvarc et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice

Zuo

Yin

Cheng

et al. 2020

Front. Cell. Neurosci.

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Pyroptosis is a recently characterized inflammatory form of programmed cell death that is thought to be involved in the pathogenesis of perioperative neurocognitive disorders (PND). Elamipretide (SS-31), a mitochondrial-targeted peptide with multiple pharmacological properties, including anti-inflammatory activity, has been demonstrated to protect against many neurological diseases. However, the effect of elamipretide on pyroptosis in PND has not been studied. We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis. Our results showed that anesthesia and surgery caused mitochondrial dysfunction and abnormal morphology, activation of canonical nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-caspase-1 dependent pyroptosis, and downregulation of synaptic integrity-related proteins in the hippocampus in aged mice, thus leading to learning and memory deficits in behavioral tests. Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits. Our results provide a promising strategy for the treatment of PND involving mitochondrial dysfunction and pyroptosis.

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“…The pathogenesis is still unclear, but risk factors such as advanced age, low baseline cognition, education level, history of DM, dehydration, malnutrition, major surgery (cardiac and orthopedic), intraoperative blood pressure fluctuation and hyperglycemia, postoperative respiratory complications, type and depth of anesthesia, etc., have been shown to contribute [ 8 ]. Anesthesia was shown to evoke a systemic and neuroinflammatory response, accumulation of Aβ proteins, increase in tau protein phosphorylation, mitochondrial dysfunction, and calcium dysregulation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Intranasal Insulin Administration to Prevent Delayed Neurocognitive Recovery and Postoperative Neurocognitive Disorder: A Narrative Review

Badenes

Qeva

Giordano

et al. 2021

IJERPH

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Delayed neurocognitive recovery and postoperative neurocognitive disorders are major complications of surgery, hospitalization, and anesthesia that are receiving increasing attention. Their incidence is reported to be 10–80% after cardiac surgery and 10–26% after non-cardiac surgery. Some of the risk factors include advanced age, level of education, history of diabetes mellitus, malnutrition, perioperative hyperglycemia, depth of anesthesia, blood pressure fluctuation during surgery, chronic respiratory diseases, etc. Scientific evidence suggests a causal association between anesthesia and delayed neurocognitive recovery or postoperative neurocognitive disorders, and various pathophysiological mechanisms have been proposed: mitochondrial dysfunction, neuroinflammation, increase in tau protein phosphorylation, accumulation of amyloid-β protein, etc. Insulin receptors in the central nervous system have a non-metabolic role and act through a neuromodulator-like action, while an interaction between anesthetics and central nervous system insulin receptors might contribute to anesthesia-induced delayed neurocognitive recovery or postoperative neurocognitive disorders. Acute or chronic intranasal insulin administration, which has no influence on the blood glucose concentration, appears to improve working memory, verbal fluency, attention, recognition of objects, etc., in animal models, cognitively healthy humans, and memory-impaired patients by restoring the insulin receptor signaling pathway, attenuating anesthesia-induced tau protein hyperphosphorylation, etc. The aim of this review is to report preclinical and clinical evidence of the implication of intranasal insulin for preventing changes in the brain molecular pattern and/or neurobehavioral impairment, which influence anesthesia-induced delayed neurocognitive recovery or postoperative neurocognitive disorders.

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Perioperative Neurocognitive Disorder

Cited by 118 publications

References 121 publications

Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Metabolomic and Lipidomic Profiling of Preoperative CSF in Elderly Hip Fracture Patients With Postoperative Delirium

Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice

Intranasal Insulin Administration to Prevent Delayed Neurocognitive Recovery and Postoperative Neurocognitive Disorder: A Narrative Review

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